BEST ix' I cm )\ (>r uuic acid 625 



been found tliat tlie (listrihution of the en/ymes mentioned above varies 

 jjreatly in tlie various organs and tissues of different species/'- In 

 most animals tiie xanthine oxidase, wliieli forms uric acid from xan- 

 thine, is localized chiefly or solely in the liver, and this is the case in 

 man ; therefore it is presumable that uric acid is formed chiefly in the 

 liver from jnirines hy the steps described above. That there may be 

 otlier metliods of foniiiiiu' uric acid is possible. 



DESTRUCTION OF URIC ACID i '• 



With most mammals but little of the total amount of purine bases 

 taken as food or set free in the tissues, appears in the urine as uric 

 acid, most of it being converted into allantoin, which seems to be ex- 

 ereted witli little or no loss. Thus, when dogs, pigs or rabbits are fed 

 nucleic acid, about 93 to 95 per cent, can be recovered as allantoin, 

 3 to 6 per cent, as uric acid, and 1 to 2 per cent, as purine bases 

 (Schittenhelm). It would seem that practically all the purines can 

 be found in these three forms combined, the proportions varying in 

 different species. In man alone, except for the chimpanzee ^* and 

 orang-utan, does a considerable proportion escape as uric acid, a fact 

 in complete harmony with repeated observation that the tissues of 

 man have no power whatever to destroy uric acid in vitro; the earlier 

 reports of positive uricolysis undoubtedly being erroneous. Even 

 the monkey has active uricolytic enzymes in its liver, and therefore 

 excretes its purines chiefly as allantoin. With mammals as a whole, 

 therefore, uric acid is destroyed to the extent of being converted into 

 allantoin,^*'' the close relationship of which to uric acid is shown by 

 the structural formula: 



NH — PH — NH 



o = i^l— i = 



I I I 



NH — CO — NH= 



(allantoin) 



With most mammals the oxidation of uric acid takes place chiefly in 

 the liver, but in some of the herbivora the kidneys are more active, as 

 far as experiments in vitro can show. 



Whether man can destroy uric acid at all has been a matter of dis- 

 pute. It has been shown by Wiechowski and others that uric acid 

 injected subcutaneouslj^ is excreted almost quantitatively and un- 

 changed in the urine. To be sure, human urine does contain a very 

 little allantoin. 7 to 14 mg. per day, but this amount is too small to be 

 of much significance, for it is possibly all derived from the food, as 



12 A compilation of this distribution is given hv Wells, Jour. PJiol. Clieni., 1010 

 (7), 171. 



13 See discussion by Wells. Jour. Lab. Clin. "Med., inio (1). 104. 



1* Wiechowski, Pras-er nied. Woch.. 1012 (37), 27o : Wells and Caldwell. .Tour. 

 Biol. Chem., 1014 (18), 157. 



14a See Hunter and Civens, .Jour. Biol. Chem., 1914 (IS), 403. 

 40 



